ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.1273C>T (p.Gln425Ter)

gnomAD frequency: 0.00001  dbSNP: rs1131691651
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494297 SCV000582560 pathogenic not provided 2016-06-10 criteria provided, single submitter clinical testing The Q393X pathogenic nonsense variant in the DYSF gene has been previously reported in patients with dysferlin deficiency, who also harbored an additional DYSF variant (Krahn et al., 2009). The Q393X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Q393X was not observed in approximately 6,500 individuals of European and African American background, indicating it is not a common benign variant in these populations. Therefore, Q393X is considered a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV003574778 SCV004292552 pathogenic Qualitative or quantitative defects of dysferlin 2024-02-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln393*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 18853459, 33610434). ClinVar contains an entry for this variant (Variation ID: 429885). For these reasons, this variant has been classified as Pathogenic.

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